Studies were carried out to attempt to understand processes for regulation and control of immune systems at the cellular level. Experiments were conducted using T-cell hybridomas as models to facilitate an understanding of regulatory mechanisms in A) the nude mouse immune system, including precursor cells and development of regulatory cell function. B) Development of regulatory cells for effector, cytotoxic T-cells (CTL). C) Modulation of T-cell function by microbial agents, e.g., streptococcal pyrogenic exotoxin (SPE). Monoclonal precursor T-cell hybridomas were constructed and cloned from antigen primed spleen cells of NFR nude mice. These clones express several T-cell markers simultaneously (TLa, Thy1, Lyt2 and Lyt3) but in variable amounts as detected by flow cytofluorometry. The clones are hyperploid and expressed the allelic markers of both parental cell types (NFR-nu spleen cells and BW5147 thymic lymphoma cells of AKR origin). Clones derived from primed Pool 1 (eluted first from nylon wool columns) nude spleen cells express a helper function and those derived from primed Pool 2 (eluted second) nude spleen cells express a suppressor function. Neither type shows immunogen-carrier specificity and are thus developmentally blocked prior to a step required for the expression of "carrier specificity." During the development of T-cell function microbial agents such as SPE could divert/change the phenotypes of these precursor T-cell hybridomas. This effect is relevant to our understanding of the mechanisms by which microorganisms modulate (deregulate) immune systems. Cytotoxic or effector (CTL) clones recognizing and reactive with self + hapten determinants have been constructed. SPE was observed to supress the function of cytotoxic effector T-cells (CTL) generated from precursors in 5 day spleen cell cultures recognizing NFR, H2q-TNP (hapten-self immunogens). The relevance of these models is that the immortal cell clones which are capable of unlimited growth and survival and expressing functional phenotypes allow for authentic and meaninbful study of pathways of regulation in immune systems and in biological systems in general. Alternative mechanisms for regulation and deviation of functions may be discovered.